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https://www.readbyqxmd.com/read/28526829/super-enhancers-and-broad-h3k4me3-domains-form-complex-gene-regulatory-circuits-involving-chromatin-interactions
#1
Fan Cao, Yiwen Fang, Hong Kee Tan, Yufen Goh, Jocelyn Yeen Hui Choy, Bryan Thean Howe Koh, Jiong Hao Tan, Nicolas Bertin, Aroul Ramadass, Ewan Hunter, Jayne Green, Matthew Salter, Alexandre Akoulitchev, Wilson Wang, Wee Joo Chng, Daniel G Tenen, Melissa J Fullwood
Stretched histone regions, such as super-enhancers and broad H3K4me3 domains, are associated with maintenance of cell identity and cancer. We connected super-enhancers and broad H3K4me3 domains in the K562 chronic myelogenous leukemia cell line as well as the MCF-7 breast cancer cell line with chromatin interactions. Super-enhancers and broad H3K4me3 domains showed higher association with chromatin interactions than their typical counterparts. Interestingly, we identified a subset of super-enhancers that overlap with broad H3K4me3 domains and show high association with cancer-associated genes including tumor suppressor genes...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28511927/coordinated-regulation-of-ifitm1-2-and-3-genes-by-an-ifn-responsive-enhancer-through-long-range-chromatin-interactions
#2
Ping Li, Ming-Lei Shi, Wen-Long Shen, Zhang Zhang, De-Jian Xie, Xiang-Yuan Zhang, Chao He, Yan Zhang, Zhi-Hu Zhao
Interferon-induced transmembrane protein (IFITM) 1, 2 and 3 are a family of interferon (IFN)-induced transmembrane proteins that block entry of a broad spectrum of pathogens. However, the transcriptional regulation of these genes, especially whether there exists any enhancers and their roles during the IFN induction process remain elusive. Here, combining episomal luciferase reporter assay and in vivo genome editing, we identified an IFNβ-responsive enhancer located 35kb upstream of IFITM3 gene promoter upregulating the IFNβ-induced expression of IFITM1, 2 and 3 genes, thus contributing to IFNβ-mediated resistance to influenza A virus (IAV) infection...
May 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28510225/controlling-gene-expression-by-dna-mechanics-emerging-insights-and-challenges
#3
REVIEW
David Levens, Laura Baranello, Fedor Kouzine
Transcription initiation is a major control point for the precise regulation of gene expression. Our knowledge of this process has been mainly derived from protein-centric studies wherein cis-regulatory DNA sequences play a passive role, mainly in arranging the protein machinery to coalesce at the transcription start sites of genes in a spatial and temporal-specific manner. However, this is a highly dynamic process in which molecular motors such as RNA polymerase II (RNAPII), helicases, and other transcription factors, alter the level of mechanical force in DNA, rather than simply a set of static DNA-protein interactions...
September 2016: Biophysical Reviews
https://www.readbyqxmd.com/read/28510218/controlling-gene-expression-by-dna-mechanics-emerging-insights-and-challenges
#4
REVIEW
David Levens, Laura Baranello, Fedor Kouzine
Transcription initiation is a major control point for the precise regulation of gene expression. Our knowledge of this process has been mainly derived from protein-centric studies wherein cis-regulatory DNA sequences play a passive role, mainly in arranging the protein machinery to coalesce at the transcription start sites of genes in a spatial and temporal-specific manner. However, this is a highly dynamic process in which molecular motors such as RNA polymerase II (RNAPII), helicases, and other transcription factors, alter the level of mechanical force in DNA, rather than simply a set of static DNA-protein interactions...
November 2016: Biophysical Reviews
https://www.readbyqxmd.com/read/28506460/mechanisms-of-ubiquitin-nucleosome-recognition-and-regulation-of-53bp1-chromatin-recruitment-by-rnf168-169-and-rad18
#5
Qi Hu, Maria Victoria Botuyan, Gaofeng Cui, Debiao Zhao, Georges Mer
The protein 53BP1 plays a central regulatory role in DNA double-strand break repair. 53BP1 relocates to chromatin by recognizing RNF168-mediated mono-ubiquitylation of histone H2A Lys15 in the nucleosome core particle dimethylated at histone H4 Lys20 (NCP-ubme). 53BP1 relocation is terminated by ubiquitin ligases RNF169 and RAD18 via unknown mechanisms. Using nuclear magnetic resonance (NMR) spectroscopy and biochemistry, we show that RNF169 bridges ubiquitin and histone surfaces, stabilizing a pre-existing ubiquitin orientation in NCP-ubme to form a high-affinity complex...
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28475873/structure-and-dynamics-of-a-197%C3%A2-bp-nucleosome-in-complex-with-linker-histone-h1
#6
Jan Bednar, Isabel Garcia-Saez, Ramachandran Boopathi, Amber R Cutter, Gabor Papai, Anna Reymer, Sajad H Syed, Imtiaz Nisar Lone, Ognyan Tonchev, Corinne Crucifix, Hervé Menoni, Christophe Papin, Dimitrios A Skoufias, Hitoshi Kurumizaka, Richard Lavery, Ali Hamiche, Jeffrey J Hayes, Patrick Schultz, Dimitar Angelov, Carlo Petosa, Stefan Dimitrov
Linker histones associate with nucleosomes to promote the formation of higher-order chromatin structure, but the underlying molecular details are unclear. We investigated the structure of a 197 bp nucleosome bearing symmetric 25 bp linker DNA arms in complex with vertebrate linker histone H1. We determined electron cryo-microscopy (cryo-EM) and crystal structures of unbound and H1-bound nucleosomes and validated these structures by site-directed protein cross-linking and hydroxyl radical footprinting experiments...
May 4, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28472433/exploring-spatially-adjacent-tfbs-clustered-regions-with-hi-c-data
#7
Hebing Chen, Shuai Jiang, Zhuo Zhang, Hao Li, Yiming Lu, Xiaochen Bo
Motivation: Transcription factor binding sites (TFBSs) are clustered in the human genome, forming the TFBS-clustered regions that regulate gene transcription, which requires dynamic chromatin configurations between promoters and distal regulatory elements. Here, we propose a regulatory model called spatially adjacent TFBS-clustered regions (SAT), in which TFBS-clustered regions are connected by spatial proximity as identified by high-resolution Hi-C data. Results: TFBS-clustered regions forming SATs appeared less frequently in gene promoters than did isolated TFBS-clustered regions, whereas SATs as a whole appeared more frequently...
May 4, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28470669/long-distance-interaction-of-the-integrated-hpv-fragment-with-myc-gene-and-8q24-22-region-up-regulating-the-allele-specific-myc-expression-in-hela-cells
#8
Congle Shen, Yongzhen Liu, Shu Shi, Ruiyang Zhang, Ting Zhang, Qiang Xu, Pengfei Zhu, Xiangmei Chen, Fengmin Lu
Human papillomavirus (HPV) infection is the most important risk factor for cervical cancer development. In HeLa cell line, the HPV viral genome is integrated at 8q24 in one allele of chromosome 8. It has been reported that the HPV fragment integrated in HeLa genome can cis-activate the expression of proto-oncogene MYC, which is located at 500 kb downstream of the integrated site. However, the underlying molecular mechanism of this regulation is unknown. A recent study reported that MYC was highly expressed exclusively from the HPV-integrated haplotype, and a long-range chromatin interaction between the integrated HPV fragment and MYC gene has been hypothesized...
May 3, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28453390/the-torments-of-the-cohesin-ring
#9
Alap P Chavda, Keven Ang, Dmitri Ivanov
Cohesin is a ring-shaped protein complex which comprises the Smc1, Smc3 and Scc1 subunits. It topologically embraces chromosomal DNA to connect sister chromatids and stabilize chromatin loops. It is required for proper chromosomal segregation, DNA repair and transcriptional regulation. We have recently reported that cohesin rings can adopt a "collapsed" rod-like conformation which is driven by the interaction between the Smc1 and Smc3 coiled coil arms and is regulated by post-translational modifications. The "collapsed" conformation plays a role in cohesin ring assembly and its loading on the DNA...
February 27, 2017: Nucleus
https://www.readbyqxmd.com/read/28451587/the-interplay-of-cofactor-interactions-and-post-translational-modifications-in-the-regulation-of-the-aaa-atpase-p97
#10
REVIEW
Petra Hänzelmann, Hermann Schindelin
The hexameric type II AAA ATPase (ATPase associated with various activities) p97 (also referred to as VCP, Cdc48, and Ter94) is critically involved in a variety of cellular activities including pathways such as DNA replication and repair which both involve chromatin remodeling, and is a key player in various protein quality control pathways mediated by the ubiquitin proteasome system as well as autophagy. Correspondingly, p97 has been linked to various pathophysiological states including cancer, neurodegeneration, and premature aging...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28447635/a-chromosome-conformation-capture-ordered-sequence-of-the-barley-genome
#11
Martin Mascher, Heidrun Gundlach, Axel Himmelbach, Sebastian Beier, Sven O Twardziok, Thomas Wicker, Volodymyr Radchuk, Christoph Dockter, Pete E Hedley, Joanne Russell, Micha Bayer, Luke Ramsay, Hui Liu, Georg Haberer, Xiao-Qi Zhang, Qisen Zhang, Roberto A Barrero, Lin Li, Stefan Taudien, Marco Groth, Marius Felder, Alex Hastie, Hana Šimková, Helena Staňková, Jan Vrána, Saki Chan, María Muñoz-Amatriaín, Rachid Ounit, Steve Wanamaker, Daniel Bolser, Christian Colmsee, Thomas Schmutzer, Lala Aliyeva-Schnorr, Stefano Grasso, Jaakko Tanskanen, Anna Chailyan, Dharanya Sampath, Darren Heavens, Leah Clissold, Sujie Cao, Brett Chapman, Fei Dai, Yong Han, Hua Li, Xuan Li, Chongyun Lin, John K McCooke, Cong Tan, Penghao Wang, Songbo Wang, Shuya Yin, Gaofeng Zhou, Jesse A Poland, Matthew I Bellgard, Ljudmilla Borisjuk, Andreas Houben, Jaroslav Doležel, Sarah Ayling, Stefano Lonardi, Paul Kersey, Peter Langridge, Gary J Muehlbauer, Matthew D Clark, Mario Caccamo, Alan H Schulman, Klaus F X Mayer, Matthias Platzer, Timothy J Close, Uwe Scholz, Mats Hansson, Guoping Zhang, Ilka Braumann, Manuel Spannagl, Chengdao Li, Robbie Waugh, Nils Stein
Cereal grasses of the Triticeae tribe have been the major food source in temperate regions since the dawn of agriculture. Their large genomes are characterized by a high content of repetitive elements and large pericentromeric regions that are virtually devoid of meiotic recombination. Here we present a high-quality reference genome assembly for barley (Hordeum vulgare L.). We use chromosome conformation capture mapping to derive the linear order of sequences across the pericentromeric space and to investigate the spatial organization of chromatin in the nucleus at megabase resolution...
April 26, 2017: Nature
https://www.readbyqxmd.com/read/28436944/active-and-poised-promoter-states-drive-folding-of-the-extended-hoxb-locus-in-mouse-embryonic-stem-cells
#12
Mariano Barbieri, Sheila Q Xie, Elena Torlai Triglia, Andrea M Chiariello, Simona Bianco, Inês de Santiago, Miguel R Branco, David Rueda, Mario Nicodemi, Ana Pombo
Gene expression states influence the 3D conformation of the genome through poorly understood mechanisms. Here, we investigate the conformation of the murine HoxB locus, a gene-dense genomic region containing closely spaced genes with distinct activation states in mouse embryonic stem (ES) cells. To predict possible folding scenarios, we performed computer simulations of polymer models informed with different chromatin occupancy features that define promoter activation states or binding sites for the transcription factor CTCF...
April 24, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28435001/hi-c-2-0-an-optimized-hi-c-procedure-for-high-resolution-genome-wide-mapping-of-chromosome-conformation
#13
Houda Belaghzal, Job Dekker, Johan H Gibcus
Chromosome conformation capture-based methods such as Hi-C have become mainstream techniques for the study of the 3D organization of genomes. These methods convert chromatin interactions reflecting topological chromatin structures into digital information (counts of pair-wise interactions). Here, we describe an updated protocol for Hi-C (Hi-C 2.0) that integrates recent improvements into a single protocol for efficient and high-resolution capture of chromatin interactions. This protocol combines chromatin digestion and frequently cutting enzymes to obtain kilobase (kb) resolution...
April 18, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28429219/effects-of-different-modes-of-hypobaric-hypoxia-on-the-content-of-epigenetic-factors-in-the-rat-in-neurons-of-rat-neocortex
#14
M O Samoilov, A V Churilova, T S Glushchenko, E A Rybnikova
We studied the effects of different modes of hypobaric hypoxia on the content of epigenetic factors acH3K24, meH3K9, and meDNA modulating conformational characteristics of chromatin and gene expression in neurons of associative complex of rat parietal neocortex. Severe destructive hypoxia dramatically reduced the level of acH3K24 in 3 h after the end of exposure and increased meH3K9 and meDNA content. By contrast, 3-fold (but not single) adaptive exposure to moderate hypobaric hypoxia that produced a neuroprotective effect enhanced neuronal acH3K24 expression and decreased both meH3K9 and meDNA levels...
April 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28426272/temperature-dependent-regulation-of-rdna-condensation-in-saccharomyces-cerevisiae
#15
Donglai Shen, Robert V Skibbens
Chromatin condensation during mitosis produces detangled and discrete DNA entities required for high fidelity sister chromatid segregation during mitosis and positions DNA away from the cleavage furrow during cytokinesis. Regional condensation during G1 also establishes a nuclear architecture through which gene transcription is regulated but remains plastic so that cells can respond to changes in nutrient levels, temperature and signaling molecules. To date, however, the potential impact of this plasticity on mitotic chromosome condensation remains unknown...
April 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28424341/alterations-in-three-dimensional-organization-of-the-cancer-genome-and-epigenome
#16
Joanna Achinger-Kawecka, Phillippa C Taberlay, Susan J Clark
The structural and functional basis of the genome is provided by the three-dimensional (3D) chromatin state. To enable accurate gene regulation, enhancer elements and promoter regions are brought into close spatial proximity to ensure proper, cell type-specific gene expression. In cancer, genetic and epigenetic processes can deregulate the transcriptional program. To investigate whether the 3D chromatin state is also disrupted in cancer we performed Hi-C chromosome conformation sequencing in normal and prostate cancer cells and compared the chromatin interaction maps with changes to the genome and epigenome...
April 19, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28420615/the-mechanism-and-clinical-significance-of-long-noncoding-rna-mediated-gene-expression-via-nuclear-architecture
#17
Shi Jian, Li Yanming, Fang Xiangdong
Long noncoding RNAs (lncRNAs) are a class of non-protein coding transcripts exceeding 200 nucleotides in length. Accumulating evidence achieved by several sophisticated techniques such as chromatin conformation capture and RNA-seq has led to new questions concerning correlations between lncRNAs and chromatin structures. Many studies have revealed that lncRNAs exert great influences on gene expression through regulating chromatin 3D structures. In addition, lncRNAs play a crucial role in tumorigenesis and therefore hold great promises in disease diagnosis and prognosis...
March 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/28402505/dicer-and-zrf1-contribute-to-chromatin-decondensation-during-nucleotide-excision-repair
#18
Shalaka Chitale, Holger Richly
Repair of damaged DNA relies on the recruitment of DNA repair factors in a well orchestrated manner. As a prerequisite, the chromatin needs to be decondensed by chromatin remodelers to allow for binding of repair factors and for DNA repair to occur. Recent studies have implicated members of the SWI/SNF and INO80 families as well as PARP1 in nucleotide excision repair (NER). In this study, we report that the endonuclease DICER is implicated in chromatin decondensation during NER. In response to UV irradiation, DICER is recruited to chromatin in a ZRF1-mediated manner...
April 10, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28388407/chromatin-architecture-emerges-during-zygotic-genome-activation-independent-of-transcription
#19
Clemens B Hug, Alexis G Grimaldi, Kai Kruse, Juan M Vaquerizas
Chromatin architecture is fundamental in regulating gene expression. To investigate when spatial genome organization is first established during development, we examined chromatin conformation during Drosophila embryogenesis and observed the emergence of chromatin architecture within a tight time window that coincides with the onset of transcription activation in the zygote. Prior to zygotic genome activation, the genome is mostly unstructured. Early expressed genes serve as nucleation sites for topologically associating domain (TAD) boundaries...
April 6, 2017: Cell
https://www.readbyqxmd.com/read/28377493/roles-of-leu28-side-chain-intercalation-in-the-interaction-between-cren7-and-dna
#20
Zhenfeng Zhang, Mohan Zhao, Li Wang, Yuanyuan Chen, Yuhui Dong, Yong Gong, Li Huang
Crenarchaeal chromatin protein Cren7 binds double-stranded DNA in the minor groove, introducing a sharp single-step DNA kink. The side chain of Leu28, a residue conserved among all Cren7 homologues, intercalates into the kink DNA step. In this study, we replaced Leu28 with a residue containing a hydrophobic side chain of different sizes (i.e., L28A, L28V, L28I, L28M and L28F). Both the stability of the Cren7-DNA complex and the ability of Cren7 to constrain DNA supercoils correlated well with the size of the intercalated side chain...
April 4, 2017: Biochemical Journal
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